This application describes the proposed transition of the HNRC from its current P50 structure to a P30 "Center of Excellence" in neuroAIDS research. Since its initial funding as an NIMH AIDS Center in 1989, the HNRC has established itself as a leader in neuroAIDS research. Its scientific stature is reflected in the several hundred publications and scientific presentations that have communicated the work of the HNRC and its associated studies on a range of multi-disciplinary topics including incidence, prevalence, and features of neurocognitive impairment (NCI); possible molecular and cellular substrates of NCI; HIV genotypic evolution in the central nervous system; the CSF as a window of CNS events; "real life" implications of NCI in terms of work, daily life, and survival: the effects of HIV disease and NCI on family and social adaptation; the therapeutics of NCI; and behavioral interventions. Evidence that the HNRC has evolved program a program whose primary focus was on performing research to one that leads and synergizes comes from the fact that the number of awards associated with the HNRC has risen from three in 1989 to 26 in 1999. In this application we envision the HNRC's development as a Center of Excellence in neuroAIDS research and education. Our aims are to (1) help identify and clarify the critical questions for neuroAIDS research; (2) determine, develop and refine the methodologies to address these; (3) enable rapid response to emerging scientific challenges and opportunities; (4) foster collaborative transdisciplinary research; (5) provide consultation and technical assistance for investigators and trainees; (6) support innovative preliminary studies; (7) provide mentorship as well as an intellectual and physical context for training; (8) facilitate information exchange relevant to neuroAIDS. Though a scientific agenda setting process we have identified scientific themes that shall be the primary (though not exclusive) focus of the research facilitated by the HNRC. These include (1) delineating the molecular mechanisms underlying HIV CNS disease; (2) exploring the CNS as a sanctuary in HIV infection and the CSF as a window to CNS events; (3) understanding cofactors that may influence neurocognitive complications; (4) determining the real life significance of NCI; (5) developing strategies for prevention and treatment of NCI. To achieve this, the HNRC will be organized as five scientific Cores- Neuromedical, Neurobehavioral, Neurobiology, Structural Neuroimaging, Cellular Immunology and Fluids-that shall provide leadership, consultation, mentoring, and practical support. A Developmental Core is proposed to help jumpstart innovative preliminary investigations as well as to mentor young scientists. An umbrella coordinating Core, consisting of Administrative, Participant Accrual and Retention, Data Management, and Statistics Units will provide the tools to synergize the efforts of the Cores and the independent research studies they are meant to facilitate. The effectiveness of the HNRC will be evaluated through internal and external review processes, including consultations with the HNRC Scientific Advisory Board, Community Advisory Board, and Participant Advisory Board.